Respiratory syncytial (RS) virus is the most common cause of respiratory tract infections in young children, and no vaccine is available. It is not known how RS virus escapes the host immune response, such that infants may be infected in the presence of transplacentally acquired antibody and reinfections occur throughout life. An understanding of the mechanisms which allow these infections would provide new perspectives for vaccine design. The attachment protein, G, is an important target of the immune response. Between the 2 major RS virus subgroups, the greatest antigenic and sequence differences occur on the G protein. The broad objective of this investigation is to characterize the molecular and antigenic heterogeneity of the RS virus attachment protein. The specific aims are: (l) To determine if antigenic changes on the G protein contribute to reinfections with the same subgroup RS virus. The G proteins of same subgroup viruses isolated during repeated infections in the same child will be analyzed for nucleotide sequence and antigenic changes. Recombinant vaccinia viruses expressing the G. proteins of pairs of these isolates will be tested for the recombinant viruses ability to protect rats against challenge by different same subgroup viruses. These studies will define the antigenic importance of G protein changes within subgroups. (2) To determine the extent of RS virus antigenic and genetic variability occurring within single epidemic periods and over time. RS viruses collected from children will be characterized by antibody reactivity, restriction fragment digestion of amplified cDNAs, and partial G gene nucleotide sequence determination. This analysis will provide data on RS virus variability to be used in vaccine planning. (3) To define the subgroup specific and cross-reactive domains of the G protein. Chimeric A/B subgroup G proteins will be produced from modified cDNAs. The antibody reactivity of the chimeras will define regions important for the maintenance of subgroup related recognition. The above studies will define the extent and importance of G protein variability and extend our understanding of G protein antigenicity. These data are directly applicable to RS virus vaccine development efforts.